5VHW

GluA2-0xGSG1L bound to ZK

5VHW の概要

• エントリーDOI: 10.2210/pdb5vhw/pdb
• 関連するPDBエントリー: 5VHX 5VHY 5VHZ
• EMDBエントリー: 8685
• 分子名称: Glutamate receptor 2,Germ cell-specific gene 1-like protein, {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: ion channel, transport protein
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 472406.69

構造登録者

Twomey, E.C.,Yelshanskaya, M.V.,Grassucci, R.A.,Frank, J.,Sobolevsky, A.I. (登録日: 2017-04-13, 公開日: 2017-05-03, 最終更新日: 2024-10-23)

主引用文献

Twomey, E.C.,Yelshanskaya, M.V.,Grassucci, R.A.,Frank, J.,Sobolevsky, A.I.
Structural Bases of Desensitization in AMPA Receptor-Auxiliary Subunit Complexes.
Neuron, 94:569-580.e5, 2017

PubMed Abstract: Fast excitatory neurotransmission is mediated by AMPA-subtype ionotropic glutamate receptors (AMPARs). AMPARs, localized at post-synaptic densities, are regulated by transmembrane auxiliary subunits that modulate AMPAR assembly, trafficking, gating, and pharmacology. Aberrancies in AMPAR-mediated signaling are associated with numerous neurological disorders. Here, we report cryo-EM structures of an AMPAR in complex with the auxiliary subunit GSG1L in the closed and desensitized states. GSG1L favors the AMPAR desensitized state, where channel closure is facilitated by profound structural rearrangements in the AMPAR extracellular domain, with ligand-binding domain dimers losing their local 2-fold rotational symmetry. Our structural and functional experiments suggest that AMPAR auxiliary subunits share a modular architecture and use a common transmembrane scaffold for distinct extracellular modules to differentially regulate AMPAR gating. By comparing the AMPAR-GSG1L complex structures, we map conformational changes accompanying AMPAR recovery from desensitization and reveal structural bases for regulation of synaptic transmission by auxiliary subunits.

PubMed: 28472657
DOI: 10.1016/j.neuron.2017.04.025

実験手法

ELECTRON MICROSCOPY (7.8 Å)